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771.
Background
Congenital cytomegalovirus (CMV) brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV) and the pattern of injury to the developing brain.Methodology/Principal Findings
We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs) and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi) cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.Conclusions
MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons. 相似文献772.
Magdalena Niedziakowska Karolina Doan Marcin Grny Maciej Sykut Krzysztof Stefaniak Natalia Piotrowska Bogumia Jdrzejewska Bogdan Ridush Sawomira Paweczyk Pawe Mackiewicz Ulrich Schmlcke Pavel Kosintsev Daniel Makowiecki Maxim Charniauski Dariusz Krasnodbski Eve Ranname Urmas Saarma Marine Arakelyan Ninna Manaseryan Vadim V. Titov Pavel Hulva Adrian Blescu Ralph Fyfe Jessie Woodbridge Katerina Trantalidou Vesna Dimitrijevi Oleksandr Kovalchuk Jarosaw Wilczyski Theodor Obad Grzegorz Lipecki Alesia Arabey Ana Stankovi 《Journal of Biogeography》2021,48(1):147-159
773.
Jiao B Ma H Shokhirev MN Drung A Yang Q Shin J Lu S Byron M Kalantry S Mercurio AM Lawrence JB Hoffmann A Bach I 《Cell》2012,149(3):630-641
In female mouse embryos, somatic cells undergo a random form of X chromosome inactivation (XCI), whereas extraembryonic trophoblast cells in the placenta undergo imprinted XCI, silencing exclusively the paternal X chromosome. Initiation of imprinted XCI requires a functional maternal allele of the X-linked gene Rnf12, which encodes the ubiquitin ligase Rnf12/RLIM. We find that knockout (KO) of Rnf12 in female mammary glands inhibits alveolar differentiation and milk production upon pregnancy, with alveolar cells that lack RLIM undergoing apoptosis as they begin to differentiate. Genetic analyses demonstrate that these functions are mediated primarily by the paternal Rnf12 allele due to nonrandom maternal XCI in mammary epithelial cells. These results identify paternal Rnf12/RLIM as a critical survival factor for milk-producing alveolar cells and, together with population models, reveal implications of transgenerational epigenetic inheritance. 相似文献
774.
Dubrova E Teslenko M 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2011,8(5):1393-1399
This paper addresses the problem of finding attractors in synchronous Boolean networks. The existing Boolean decision diagram-based algorithms have limited capacity due to the excessive memory requirements of decision diagrams. The simulation-based algorithms can be applied to larger networks, however, they are incomplete. We present an algorithm, which uses a SAT-based bounded model checking to find all attractors in a Boolean network. The efficiency of the presented algorithm is evaluated by analyzing seven networks models of real biological processes, as well as 150,000 randomly generated Boolean networks of sizes between 100 and 7,000. The results show that our approach has a potential to handle an order of magnitude larger models than currently possible. 相似文献
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777.
Pavel Merkulov Sofya Gvaramiya Maxim Dudnikov Roman Komakhin Murad Omarov Alina Kocheshkova Zakhar Konstantinov Alexander Soloviev Gennady Karlov Mikhail Divashuk Ilya Kirov 《植物学报(英文版)》2023,65(10):2242-2261
Transposable element insertions (TEIs) are an important source of genomic innovation by contributing to plant adaptation, speciation, and the production of new varieties. The often large, complex plant genomes make identifying TEIs from short reads difficult and expensive. Moreover, rare somatic insertions that reflect mobilome dynamics are difficult to track using short reads. To address these challenges, we combined Cas9-targeted Nanopore sequencing (CANS) with the novel pipeline NanoCasTE to trace both genetically inherited and somatic TEIs in plants. We performed CANS of the EVADÉ (EVD) retrotransposon in wild-type Arabidopsis thaliana and rapidly obtained up to 40× sequence coverage. Analysis of hemizygous T-DNA insertion sites and genetically inherited insertions of the EVD transposon in the ddm1 (decrease in DNA methylation 1) genome uncovered the crucial role of DNA methylation in shaping EVD insertion preference. We also investigated somatic transposition events of the ONSEN transposon family, finding that genes that are downregulated during heat stress are preferentially targeted by ONSENs. Finally, we detected hypomethylation of novel somatic insertions for two ONSENs. CANS and NanoCasTE are effective tools for detecting TEIs and exploring mobilome organization in plants in response to stress and in different genetic backgrounds, as well as screening T-DNA insertion mutants and transgenic plants. 相似文献
778.
Maxim E. Sergeev Tatiana L. Voyushina 《Journal of Molecular Catalysis .B, Enzymatic》2010,62(1):104-106
An efficient and straightforward proteolytic enzyme-catalyzed approach towards the regioselective synthesis of nucleopeptides was developed. Appropriate reaction conditions were investigated and certain peptide-modified nucleosides were obtained with 70–90% yields. The obtained compounds could be efficiently used for medicinal diagnostic kits and therapeutic treatment. 相似文献
779.
Andrei V. Bogdanov Kamilla R. Iskhakova Alexandra D. Voloshina Anastasia S. Sapunova Natalia V. Kulik Natalia V. Terekhova Maxim V. Arsenyev Guzel K. Ziyatdinova Sergey V. Bukharov 《化学与生物多样性》2020,17(5)
The increase in the resistance of pathogens, in particular Staphylococcus aureus, to the action of antibiotics necessitates the search for new readily available and non‐toxic drugs. In solving this problem, phenolic acylhydrazones have high potential. In this communication, the synthesis of quaternary ammonium compounds containing a differently substituted phenolic moiety has been performed. An initial study of antimicrobial activity showed that these compounds are highly selective against S. aureus and B. cereus. The highest activity (MIC 2.0 μm ) was shown by hydrazones containing a catechol fragment. These compounds are more than 3‐fold more active against S. aureus and 3–10‐fold more active against B. cereus than norfloxacin. Low hemolytic and high antioxidant activities of all new compounds were also established. 相似文献
780.
Gasparian ME Bychkov ML Dolgikh DA Kirpichnikov MP 《Protein expression and purification》2011,79(2):191-196
Enteropeptidase (synonym: enterokinase, EC 3.4.21.9) is a heterodimeric serine protease of the intestinal brush border that activates trypsinogen by highly specific cleavage of the trypsinogen activation peptide following the sequence (Asp)(4)-Lys. It has also great biotechnological interest because of the unique substrate specificity of the serine protease domain. The high degree of specificity exhibited by enteropeptidase makes it a suitable reagent for cleaving recombinant proteins to remove affinity or other tags. However often unwanted cleavages elsewhere in the protein occurred during cleavage of fusions when high amount of enzyme is required. In this study we have improved the efficiency of fusion proteins cleavage by enteropeptidase by substitution of the Lys residue by Arg in specific cleavage sequence (Asp)(4)-Lys. We have demonstrated that 3-6-fold lower amounts of the catalytic subunit of human and bovine enteropeptidase is required for 95% cleavage of Trx/TRAIL and Trx/FGF-2 fusions with (Asp)(4)-Arg cleavage sequence in comparison to native sequence (Asp)(4)-Lys. As a result, reduced amount of non-specifically cleaved peptide fragments were observed during cleavage of (Asp)(4)-Lys/Arg mutated fusions. These findings overcome limitations of enteropeptidase in tag removal processes during recombinant proteins purification and extend its commercial benefit in the biopharmaceutical industry. 相似文献